Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 µg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.

Segmental motion at the peak of the ossification foci is independent risk factor except for mal-alignment and thick ossification foci for poor outcome after laminoplasty for cervical ossification of the posterior longitudinal ligament: analyses in patients with positive K-line, lordotic alignment, and lower canal occupying ratio.

PURPOSE: To elucidate the independent preoperative factors that have a significant impact on poor surgical outcome after laminoplasty for K-line (+) ossification of the posterior longitudinal ligament (OPLL). Analyses in K-line (+) patient population can exclude the influence by mal-alignment and thick OPLL, both of which are well known two major factors that have significant impact on clinical outcome. METHODS: The present study included 72 patients (50 male and 22 female) who underwent laminoplasty for K-line (+) cervical OPLL and were followed-up for at least 1 year. Recovery of Japanese Orthopedic Association score (JOA score) for cervical myelopathy was used as the measure of clinical outcome. For radiographic assessment, the type of OPLL, the maximum OPLL occupation ratio, the C2-C7 angle, and the segmental range of motion at the peak of OPLL (segmental ROM) were assessed. To elucidate the factors that are significantly associated with a poor clinical outcome after laminoplasty for K-line (+) OPLL, statistical analyses were conducted. RESULTS: The mean preoperative JOA score was 8.9 points and improved to 12.8 points after surgery. The recovery of JOA score was 47 ± 35%. Stepwise logistic regression following univariate analyses revealed that preoperative segmental ROM at the peak of OPLL is an independent factor associated with a poor outcome (p = 0.04, odds ratio = 1.15). CONCLUSIONS: Large preoperative segmental ROM at the peak of the OPLL is an independent factor that has significant impact on poor surgical outcome after laminoplasty for K-line (+) OPLL.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. METHODS AND ANALYSIS: The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). ETHICS AND DISSEMINATION: The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. TRIAL REGISTRATION NUMBER: UMIN000018752.

Retrospective exploration of risk factors for L5 radiculopathy following lumbar floating fusion surgery.

BACKGROUND: Lumbar floating fusion occasionally causes postoperative adjacent segment disorder (ASD) at lumbosacral level, causing L5 spinal nerve disorder by L5-S1 foraminal stenosis. The disorder is considered to be one of the major outcomes of L5-S1 ASD, which has not been evaluated yet. The present study aimed to evaluate the incidence and risk factors of postoperative L5 spinal nerve disorder after lumbar interbody fusion extending to the L5 vertebra. METHODS: We evaluated 125 patients with a diagnosis of spondylolisthesis who underwent floating fusion surgery with transforaminal lumbar interbody fusion with average postoperative period of 25.2 months. The patients were regarded as symptomatic with postoperative L5 spinal nerve disorder such as radicular pain/numbness in the lower limbs and/or motor dysfunction. We estimated and compared the wedging angle (frontal view) and height (lateral view) of the lumbosacral junction in pre- and postoperative plain X-ray images and the foraminal ratio (ratio of the narrower foraminal diameter to the wider diameter in the craniocaudal direction) in the preoperative magnetic resonance image. Risk factors for the incidence of L5 spinal nerve disorder were explored using multivariate logistic regression. RESULTS: Eight of the 125 patients (6.4%) were categorized as symptomatic, an average of 13.3 months after surgery. The wedging angle was significantly higher, and the foraminal ratio was significantly decreased in the symptomatic group (both P < 0.05) compared to the asymptomatic group. Multivariate logistic regression analysis of possible risk factors revealed that the wedging angle, foraminal ratio, and multileveled fusion were statistically significant. CONCLUSIONS: Higher wedging angle and lower foraminal ratio in the lumbosacral junction were significantly predictive for the incidence of L5 nerve root disorder as well as multiple-leveled fusion. These findings indicate that lumbosacral fixation should be considered for patients with these risk factors even if they have few symptoms from the L5-S1 junction.

Failure of conservative treatment for thoracic spine fracture in ankylosing spondylitis: delayed neurological deficit due to spinal epidural hematoma.

Patients with ankylosing spondylitis (AS) are prone to spinal fracture after even minor trauma. We report a case of thoracic spinal fracture in a patient with AS who developed a secondary neurological deficit due to delayed diagnosis and prolonged conservative treatment. When the neurological deficit occurred, the fractured segment showed no displacement, but a spinal epidural hematoma was present. Surgical treatment produced significant neurological improvement, although incomplete paralysis persisted.

A prospective randomized controlled study comparing transforaminal lumbar interbody fusion techniques for degenerative spondylolisthesis: unilateral pedicle screw and 1 cage versus bilateral pedicle screws and 2 cages.

OBJECT: Many surgeons currently prefer to use transforaminal lumbar interbody fusion (TLIF), placing 1 unilateral pedicle screw (PS) and 1 cage. However, no study has examined whether unilateral fixation improves surgical outcome. The authors conducted a prospective randomized controlled trial with a minimum 2-year follow-up to analyze TLIF outcomes for 2 techniques: placement of a unilateral PS and a cage compared with placement of bilateral PSs and 2 cages. METHODS: Fifty patients with degenerative spondylolisthesis undergoing single-level TLIF were randomly assigned to receive either unilateral or bilateral fixation. Parameters compared between the groups were surgical invasiveness, severity of intermittent claudication, pre- and postoperative visual analog scale (VAS) scores (from 0 to 10 for back pain, lower-extremity pain, and lower-extremity numbness), postoperative disability scores for lumbar spinal disorders (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire [JOABPEQ]), and fusion rates. RESULTS: The mean operative time for TLIF was significantly (p = 0.05) shorter and mean estimated blood loss was significantly lower in the unilateral than in the bilateral group. Intermittent claudication improved in response to each technique, but there was no significant intergroup difference. The unilateral group had a nonsignificant tendency toward less improvement in VAS score for back pain (1.5 vs 3.7 for the bilateral group) and exhibited significantly less improvement in VAS score for lower-extremity pain (2.1 vs 5.1, respectively) and numbness (1.7 vs 4.4). There were no significant differences between the groups in postsurgical scores for all 5 items of the JOABPEQ. The fusion rates were 87.5% (21 of 24 patients) in the unilateral group and 95.7% (22 of 23) in the bilateral group. CONCLUSIONS: Transforaminal lumbar interbody fusion involving unilateral PS fixation and a single-cage technique is less invasive than a 2-cage technique and bilateral fixation, and it improved patients' symptoms. However, it resulted in less improvement in back pain, lower-extremity pain, and lower-extremity numbness. When considering unilateral PS fixation and a single cage, the surgeon should be aware of the potential limitations of this technique. Clinical trial registration no.: UMIN000007833 (UMIN).

An unusually rapid spontaneous recovery in a patient with spinal epidural hematoma.

BACKGROUND: Spontaneous epidural hematoma is a rare condition, which usually requires urgent surgical treatment. OBJECTIVES: To report two cases of spontaneous epidural hematoma, one of which was treated conservatively, and the other surgically, and discuss the possibility of unusual spontaneous recovery and treatment decision-making. CASE REPORT: We encountered 2 patients with spontaneous spinal epidural hematoma, both of whom were taking an anti-platelet agent, producing severe paraplegia. One patient with a hematoma at C2-T3 experienced a rapid neurological recovery while a magnetic resonance imaging scan was being performed. A complete resolution of the hematoma and complete neurological recovery ensued without surgical intervention. A second patient with a hematoma at T10-12 showed no neurological recovery up to the time emergency surgery started and was treated surgically by T10-12 laminectomy and excision of the hematoma. Neurological function returned to normal in both patients. CONCLUSION: The occurrence of spontaneous recovery in some patients makes the decision for surgery difficult. Emergency physicians need to be aware of the possibility of spontaneous rapid neurological recovery in patients with spinal epidural hematoma. To avoid unnecessary surgery in patients who will spontaneously have neurological recovery, neurological evaluations need to be repeatedly performed up to the time the emergency surgery begins. However, unfortunately, there is no diagnostic tool at present to identify the patients who recover spontaneously, and the interval between onset and surgery is correlated with clinical results, therefore, conservative treatment should be prescribed only for those patients who exhibit improving neurological signs early in the clinical course.

Association between serum leptin and bone metabolic markers, and the development of heterotopic ossification of the spinal ligament in female patients with ossification of the posterior longitudinal ligament.

Obesity is a risk factor for ossification of the posterior longitudinal ligament (OPLL) of the spine, which is characterized by heterotopic bone formation in the posterior longitudinal spinal ligament. Hyperleptinemia is a common feature of obese people and leptin is believed to be an important factor in the pathogenesis of OPLL. However, the association between leptin and bone metabolism and the development of OPLL is not understood fully. The objective of the present study was to determine the association between serum leptin concentration and bone metabolic markers and the extent of heterotopic ossification of the spinal ligament in patients with OPLL. The serum concentrations of leptin, insulin, fructosamine, bone-specific alkaline phosphatase, and carboxyterminal propeptide of type I procollagen, urine deoxypyridinoline levels, and the number of vertebrae with OPLL involvement were measured in 125 (68 males and 57 females) patients with OPLL. The correlation between leptin and these other factors was then examined. Serum leptin and insulin concentrations were increased significantly in OPLL females compared to non-OPLL female controls. In the females with OPLL, serum leptin concentrations corrected for body mass index correlated positively with the number of vertebrae with OPLL involvement. In females, serum leptin levels were significantly higher in patients in whom OPLL extended to the thoracic and/or lumbar spine than in patients in whom OPLL was limited to the cervical spine. Our results suggest that hyperleptinemia, in combination with hyperinsulinemia, may contribute to the development of heterotopic ossification of the spinal ligament in female patients with OPLL.

Examining risk factors for posterior migration of fusion cages following transforaminal lumbar interbody fusion: a possible limitation of unilateral pedicle screw fixation.

OBJECT: Because the authors encountered 4 cases of hardware migration following transforaminal lumbar interbody fusion, a retrospective study was conducted to identify factors influencing the posterior migration of fusion cages. METHODS: Patients with lumbar degenerative disc disease (125 individuals; 144 disc levels) were treated using transforaminal lumbar interbody fusion and followed for 12-33 months. Medical records and pre- and postoperative radiographs were reviewed, and factors influencing the incidence of cage migration were analyzed. RESULTS: Postoperative cage migration was found in 4 patients at or before 3 months. Because all the cages that migrated postoperatively were bullet-shaped (Capstone), only these cages were analyzed. The analysis of preoperative radiographs revealed that higher posterior disc height ([PDH] > or = 6 mm) significantly increased the incidence of postoperative cage migration, but percent slippage, translation, range of motion, and Cobb angle did not. The incidence of cage migration in patients with unilateral fixation (3 [8.3%] of 36) was not significantly different from that in patients with bilateral fixation (1 [2.1%] of 48). Patients who had scoliotic curvature with a Cobb angle > 10 degrees when treated with unilateral fixation demonstrated a tendency to have more frequent postoperative cage migration than patients treated with bilateral fixation. To examine the influence of the height of fusion cages, a value obtained by subtracting preoperative anterior disc height (ADH) or PDH from cage height was defined as "Cage height - ADH" (or "Cage height -PDH"). The analysis revealed that the value for "Cage height -ADH" as well as "Cage height -PDH" was significantly lower in migrated levels than in nonmigrated levels, suggesting that the choice of undersized cages may increase the incidence of cage migration. CONCLUSIONS: The results suggest that the use of a bullet-shaped cage, higher PDH, the presence of scoliotic curvature, and undersized fusion cages are possible risk factors for cage migration. One patient with postoperative cage migration following bilateral screw fixation underwent revision surgery, and the pedicle screw fixation was found to be disrupted. Other than in this patient, cage migration occurred only in those treated by unilateral fixation. The potential for postoperative cage migration and limitations of unilateral fixation should be considered by spine surgeons.

Comparison of early and late surgical intervention for lumbar disc herniation: is earlier better?

BACKGROUND: The optimal timing for surgical intervention in cases of lumbar disc herniation is debatable. This retrospective study sought to determine whether early surgical intervention resulted in greater improvement in clinical outcomes. METHODS: A total of 46 patients with lumbar disc herniation treated by microendoscopic discectomy were reviewed. Surgery was performed when leg pain persisted despite adequate conservative treatment. The patients were divided into two groups according to the duration of symptoms before surgery, the early group being symptomatic for 3 months. Surgical time, blood loss, severity of back pain, leg pain and numbness (visual analogue scale, or VAS), and a patient-oriented evaluation score (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, or JOABPEQ) before and after surgery were compared. The JOABPEQ is a new evaluation method for lumbar spinal disorders based on Roland-Morris disability questionnaires and Short Form 36. RESULTS: There were 23 patients in each group. No significant differences were found between the groups in patients' demographics (age, sex, type of herniation), surgical time, blood loss, or pre- and postoperative VAS (lower-back pain, leg pain, numbness). There were no significant differences between the groups in the scores for the five subscales - pain-related disorders, gait disturbance, lumbar spine dysfunction, social life disturbance, psychological disorders - of the preoperative JOABPEQ. Postoperative scores for psychological disorders improved significantly (P < 0.05) in the late group (mean score 39.9) compared to the early group (mean score 22.1). Interestingly, no significant difference of improvement in the scores other than psychological disorder was found between the two groups. CONCLUSIONS: Early surgical intervention did not result in greater improvement of clinical outcomes for patients with lumbar disc herniation. Later surgical intervention resulted in significant improvement of psychological disorders.

[Incidence and clinical features of anaphylaxis during general anesthesia].

BACKGROUND: Anaphylaxis is an acute life-threatening systematic reaction, and it requires early diagnosis and correct management to save the patients. The true incidence of anaphylaxis during general anesthesia is unknown. Although anaphylaxis is a rare intraoperative complication, most drugs used in the perioperative period can lead to anaphylaxis. METHODS: All patients who had received operations under general anesthesia in our hospital were covered in this study during the 5-year period. We searched for the incidence and clinical features of anaphylaxis retrospectively. RESULTS: Seven cases in 9,844 patients were recognized. Various drugs were suspected as causal agents, but they were all nonanesthesia related drugs. The diagnosis of anaphylaxis relied on the history and clinical course of each patient. There was no reliable diagnostic testing such as serum tryptase and skin test. So we could not determine whether the reaction was IgE-mediated or not. CONCLUSIONS: Immediate discontinuation of causal drugs and early administration of epinephrine are cornerstones of treatment. More specific diagnostic tests are required for correct identification of causal drugs. To reduce the risk of anaphylaxis during anesthesia, we hope practical data bases and guidelines for anaphylaxis related to anesthesia will be published in the future.

An unusual cause of sciatic pain as a result of the dynamic motion of the obturator internus muscle.

BACKGROUND CONTEXT: It has been reported that compression of the sciatic nerve because of any cause, including endometriosis, piriformis syndrome, abscess, tumor, adjoining uterus provoke sciatic pain. Some of these pathophysiologies have been diagnosed clinically and sometimes by exclusion. PURPOSE: To discuss the clinical features of sciatic neuropathy under the belief that dynamic motion of the obturator internus muscle and tendon should be included in the differential diagnosis of sciatic neuropathy. STUDY DESIGN: Sciatic neuropathy, which was because of compression of the sciatic nerve caused by dynamic motion of the tendon and muscle of the obturator internus, was reported. METHODS: We performed surgery to confirm the outlet of the pelvis. RESULTS: Although no compression was provoked by the piriformis muscle, obvious compression was observed on the sciatic nerve by the stretched obturator internus muscle. CONCLUSIONS: Although it may not be common, compression of the sacral plexus caused by dynamic motion of the obturator internus muscle should be included as a possible diagnosis for sciatic pain.

Posterior migration of fusion cages in degenerative lumbar disease treated with transforaminal lumbar interbody fusion: a report of three patients.

STUDY DESIGN: A case report of 3 patients with posterior migration of bullet-shaped fusion cages after transforaminal lumbar interbody fusion (TLIF). One patient required emergency revision surgery; the other 2 patients are being observed during conservative treatment. OBJECTIVE: To review cases of posterior migration of fusion cages and report ensuing clinical courses. SUMMARY OF BACKGROUND DATA: TLIF is a commonly used procedure; however, there are few reports describing cage migration after the procedure. In most cases, when posterior cage migration follows posterior lumbar interbody fusion, emergency revision surgery is required. One recent study reported a case of posterior cage migration after TLIF, which was treated conservatively. METHODS: Posterior migration of the bullet-shaped fusion cages occurred 1 to 2 months after TLIF in 3 patients. One of the 3 patients had isthmic spondylolisthesis treated by TLIF with bilateral pedicle screw fixation. The other 2 patients had degenerative scoliosis and were treated by TLIF with unilateral pedicle screw fixation. RESULTS: The patient with isthmic spondylolisthesis required revision surgery because the migrated cage caused nerve root irritation. The migrated cage was removed and a large-sized cage was employed to achieve stability. The other 2 patients had no pathologic symptoms after the posterior migration of the cage and were treated conservatively and observed. CONCLUSION: Revision surgery after TLIF appears relatively safe because the migrated cage tends to locate more laterally than in patients with cage migration after posterior lumbar interbody fusion. Cage migration subsequent to TLIF may not cause compression of neural tissues, so conservative treatment may suffice for these patients. Unilateral pedicle screw fixation may not provide sufficient stability to prevent cage migration in patients with degenerative scoliosis. Further study is needed to clarify surgical indications for unilateral pedicle screw fixation in TLIF.

Clinical results of surgery for thoracic myelopathy caused by ossification of the posterior longitudinal ligament: operative indication of posterior decompression with instrumented fusion.

STUDY DESIGN: This retrospective study was conducted to investigate the clinical outcomes of several surgical procedures for thoracic myelopathy caused by ossification of the posterior longitudinal ligament (OPLL). OBJECTIVE: To evaluate the effect of myelopathy treatment and safety of posterior decompression with instrumented fusion. SUMMARY OF BACKGROUND DATA: Many different surgical procedures have been used for the treatment of thoracic OPLL. However, the possibility of postoperative paraplegia remains a major risk, and consistent protocols and procedures for surgical treatment of thoracic OPLL have also not been established. METHODS: A total of 51 patients who underwent surgery for thoracic OPLL were classified into 3 groups: (1) posterior decompression group (18 patients), which included 12 who underwent laminectomy and 6 who underwent cervicothoracic laminoplasty; (2) OPLL extirpation group (16 patients), which included 4 who underwent anterior decompression through thoracotomy and 12 who underwent anterior decompression through the posterior approach; and (3) posterior decompression and fusion group (17 patients), all of whom underwent laminectomy with posterior instrumented fusion. In each group, the Japanese Orthopedic Association score was used to evaluate thoracic myelopathy, and the recovery rate calculated 1 year after surgery and at final examination. RESULTS: Mean recovery rate at final follow-up was 41.9% in the posterior decompression group, 62.1% in the OPLL extirpation group, and 59.3% in the posterior decompression and fusion group. Postoperative paralysis occurred in 3 patients in the posterior decompression group and in 3 in the OPLL extirpation group. In the OPLL extirpation group, leakage of cerebrospinal fluid occurred in 8 patients and hydrothorax in 2. Late neurologic deterioration occurred in 7 patients in the posterior decompression group. There were no cases of postoperative paralysis or late neurologic deterioration in the posterior decompression and fusion group. CONCLUSIONS: A considerable degree of neurologic recovery was obtained by posterior decompression with instrumented fusion, despite the anterior impingement of the spinal cord by OPLL remaining. In addition, the rate of postoperative complications was extremely low with this procedure. We recommend that 1-stage posterior decompression and instrumented fusion be selected for patients in whom the spinal cord is severely damaged before surgery and/or when extirpation of OPLL is associated with increased risk.

Relationship between low-back pain, muscle spasm and pressure pain thresholds in patients with lumbar disc herniation.

It is not known whether or not muscle spasm of the back muscles presented in patients with sciatic scoliosis caused by lumbar disc herniation produces muscle pain and/or tenderness. Pressure pain thresholds (PPTs) of the lower back and low-back pain were examined in 52 patients (13 of 52 presenting sciatic scoliosis) with lumbar disc herniation who complained of radicular pain and in 15 normal subjects. PPTs were measured at five points bilaterally using an electronic pressure algometer. Low-back pain was evaluated using visual analogue scale (VAS) ratings. All patients complained of radicular leg pain and were divided into the following three groups according to the presence of and the region of low-back pain: no low-back pain group, low-back pain with no laterality group, and low-back pain dominantly on the herniation side group; the VAS rating on the side ipsilateral to the herniation side was higher than that on the contralateral side. In the normal subjects, there were no statistically significant differences between sides in mean PPTs at all sites examined. PPTs were not lower in the spasmodic side (concave side) than the convex side in patients with sciatic scoliosis. PPTs on the herniation side were significantly lower than those on the contralateral side in patients with low-back pain dominantly on the herniation side. Furthermore, the areas of low PPTs were beyond the innervation area of dorsal ramus of L5 and S1 nerve root. It was considered that not only the peripheral mechanisms but also the hyper excitability of the central nervous system might contribute in lowering PPTs of the lower back on the herniation side.

[Lumbar epidural morphine for postoperative analgesia in children undergoing Nuss procedure].

BACKGROUND: We examined the effects of lumbar epidural morphine for postoperative analgesia in children after the Nuss procedure for funnel chest. METHODS: An epidural catheter was inserted from the L 3-4 interspace preoperatively (epidural group). Epidural morphine 30 microg x kg(-1) was given at the beginning of the operation. Postoperatively, epidural morphine 3 microg x kg(-1) x hr(-1) was infused. The frequency of demand for postoperative analgesia was retrospectively compared with that of children who had not received epidural morphine (control group). RESULTS: On the 0th postoperative day, the epidural group required fewer analgesics than the control group (0.50+/-0.30 vs. 2.50+/-1.00 x day(-1)). However, after the 1st postoperative day, the demand for analgesia did not differ between the two groups. CONCLUSIONS: Epidural morphine 30 microg x kg(-1) given at the beginning of operation provided effective analgesia on the 0th postoperative day after the Nuss procedure. However, epidural infusion of morphine 3 microg x kg(-1) x hr(-1) was not effective after the 1st postoperative day. Further study is needed to determine the lumbar epidural infusion dose of morphine adequate for use after the Nuss procedure.

The extent of ossification of posterior longitudinal ligament of the spine associated with nucleotide pyrophosphatase gene and leptin receptor gene polymorphisms.

STUDY DESIGN: A case-control study using radiograph findings and the PCR assay with regard to the susceptibility and the severity of ossification of posterior longitudinal ligament of the spine (OPLL). OBJECTIVE: To analyze whether polymorphisms of the nucleotide pyrophosphatase (NPPS) gene and the leptin receptor gene predispose to an increased frequency and severity of OPLL. SUMMARY OF BACKGROUND DATA: The NPPS gene is responsible for ectopic ossification in the ttw mouse, an animal model for OPLL. The Zucker fatty rat, another animal model for OPLL, has a missense mutation in the leptin receptor gene. METHODS: Analysis of 172 OPLL patients and 93 non-OPLL controls was performed. Radiographs of the cervical, thoracic and lumber spine were analyzed to determine whether OPLL was present and to what degree. Genomic DNA was extracted from all participants. Polymorphisms of the NPPS gene and the leptin receptor gene were analyzed using the PCR assay. The association of the polymorphisms with the development and extent of OPLL were statistically evaluated. RESULTS: No significant association was found between the polymorphisms and the existence of OPLL in both the NPPS and the leptin receptor genes. However, the IVS20-11delT variant in the NPPS gene and the A861G variant in the leptin receptor gene were more frequent in patients with OPLL in the thoracic spine compared with patients whose OPLL was restricted to the cervical spine. CONCLUSION: The present results suggest that the IVS20-11delT variant of the NPPS gene and the A861G variant of the leptin receptor gene are associated with more extensive OPLL, but not with the frequency with which it occurs.

Epidural clonidine suppresses the baroreceptor-sympathetic response depending on isoflurane concentrations in cats.

Epidural administration of clonidine induces hypotension and bradycardia secondary to decreased sympathetic nerve activity. In this study, we sought to elucidate the change in baroreflex response caused by epidural clonidine. Thirty-six cats were allocated to six groups (n = 6 each) and were given either thoracic epidural clonidine 4 micro g/kg or lidocaine 2 mg/kg during 0.5, 1.0, or 1.5 minimum alveolar anesthetic concentration (MAC) isoflurane anesthesia. Heart rate (HR), mean arterial blood pressure (MAP), and cardiac sympathetic nerve activity (CSNA) were measured. Depressor and pressor responses were induced by IV nitroprusside 10 micro g/kg and phenylephrine 10 micro g/kg, respectively. Baroreflex was evaluated by the change in both CSNA and HR relative to the peak change in MAP (deltaCSNA/deltaMAP and deltaHR/deltaMAP, respectively). These measurements were performed before and 30 min after epidural drug administration. Epidural clonidine and lidocaine decreased HR, MAP, and CSNA by similar extents. deltaCSNA/deltaMAP and deltaHR/deltaMAP for depressor response were suppressed with epidural lidocaine and clonidine in all groups but the clonidine 0.5 MAC isoflurane group (0.197 +/- 0.053 to 0.063 +/- 0.014 and 0.717 +/- 0.156 to 0.177 +/- 0.038, respectively, by epidural lidocaine [P < 0.05] but 0.221 +/- 0.028 to 0.164 +/- 0.041 and 0.721 +/- 0.177 to 0.945 +/- 0.239, respectively, by epidural clonidine during 0.5 MAC isoflurane). Those for pressor response were suppressed in all groups. We conclude that thoracic epidural clonidine suppresses baroreflex gain during isoflurane anesthesia >1.0 MAC but may offer certain advantages compared with epidural lidocaine during 0.5 MAC isoflurane by virtue of preserving baroreflex sensitivity when inadvertent hypotension occurs.

[A case of multiple skin metastases from gastric cancer successfully treated with docetaxel combined with doxifluridine].

The results of treatment of gastric cancer with docetaxel have scarcely been reported. Combination chemotherapy of docetaxel and doxifluridine was administered to five patients with recurrent or unresectable gastric cancer in the authors' department, and the overall response rate was 40%. Among them, we report here a case of multiple skin metastases successfully treated with this chemotherapy. A 71-year-old man had already undergone total gastrectomy with splenectomy about one year previously because of advanced gastric cancer: type 3, tub2, se, n1, INF gamma, ly3(+), v1(+), stage IIIa. He was treated with adjuvant chemotherapy of low-dose FP (CDDP/5-FU) for two weeks, and thereafter 5-FU (200 mg/day orally) was administered. Skin metastases appeared on the right upper eyelid and the left femoral region, though no recurrent findings were detected by CT, US, and the like one year after operation. The combination chemotherapy of docetaxel and doxifluridine was administered because multiple skin tumors rapidly appeared on the back and the right upper eyelid region. These tumors disappeared after 3 weeks and he has had no recurrence more than one year after chemotherapy.